物理化学学报 >> 2016, Vol. 32 >> Issue (7): 1810-1818.doi: 10.3866/PKU.WHXB201604145

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过氧钒配合物抑制朊蛋白淀粉样肽的纤维形成

张宝红1,2,胡国胜1,*(),朱登森2,王文姬2,巩格辉2,杜为红2,*()   

  1. 1 中北大学材料科学与工程学院,太原030051
    2 中国人民大学化学系,北京100872
  • 收稿日期:2016-02-29 发布日期:2016-07-08
  • 通讯作者: 胡国胜,杜为红 E-mail:chinahugsh@hotmail.com;whdu@ruc.edu.cn
  • 基金资助:
    国家自然科学基金(21271185);国家自然科学基金(21473251)

Inhibition of Prion Amyloid Peptide Fibril Formation by Peroxovanadium Complexes

Bao-Hong ZHANG1,2,Guo-Sheng HU1,*(),Deng-Sen ZHU2,Wen-Ji WANG2,Ge-Hui GONG2,Wei-Hong DU2,*()   

  1. 1 College of Materials Science and Engineering,North University of China,Taiyuan 030051,P.R.China
    2 Department of Chemistry,Renmin University of China,Beijing 100872,P.R.China
  • Received:2016-02-29 Published:2016-07-08
  • Contact: Guo-Sheng HU,Wei-Hong DU E-mail:chinahugsh@hotmail.com;whdu@ruc.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(21271185);National Natural Science Foundation of China(21473251)

摘要:

采用荧光光谱(FS)、核磁共振(NMR)、电喷雾离子化质谱(ESI-MS)和透射电镜(TEM)方法研究过氧钒配合物(NH4)[VO(O2)2(bipy)]·4H2O(1)和(NH4)[VO(O2)2(phen)]·2H2O(2)与朊蛋白淀粉样肽PrP106-126的突变体M109F肽的相互作用。结果表明,过氧钒配合物可直接与M109F肽结合,并通过甲硫氨酸112的氧化作用来达到对M109F肽聚集的抑制作用。与配合物2比较,配合物1显示出对M109F肽更好的抑制作用;过氧钒配合物12都可以有效地降低M109F肽诱导的细胞毒性。本工作为潜在金属药物用于神经退行性疾病的研究提供了基础数据。

关键词: 朊蛋白神经肽, 过氧钒配合物, 纤维化, 甲硫氨酸氧化, 细胞毒性

Abstract:

Interactions of peroxovanadiumcomplexes(NH4)[VO(O2)2(bipy)]·4H2O(1)and(NH4)[VO(O2)2(phen)]·2H2O(2)with the mutant peptide M109F of prion neuropeptide PrP106-126 have been investigated by fluorescence spectroscopy(FS),nuclear magnetic resonance(NMR),electron spray ionization mass spectrometry(ESI-MS)and transmission electron microscopy(TEM)methods.The results show that the peroxovanadium complexes may directly bind to the M109F peptide,and react with the peptide by methionine oxidation at Met112,resulting in the inhibition of M109F peptide aggregation.Compared with complex 2,complex 1 shows improved inhibitory effects on peptide M109F.Both complexes 1 and 2 exhibit an increased cellular viability against amyloid peptide-induced cytotoxicity.The basic data for the investigation of potential metallodrugs against neurodegenerative disease are provided.

Key words: Prion neuropeptide, Peroxovanadium complex, Fibril formation, Methionine oxidation, Cytotoxicity

MSC2000: 

  • O641